The proposed research is designed to define the relationship between cation content, cation transport, and energy production (glycolysis and tricarboxcylic acid cycle (TCA) activity) and phytohemagglutinin stimulated blastic transformation in normal and leukemic lymphocytes. The relative contributions of glycolysis and TCA activity to ATP stability will be assessed through the use of selective metabolic inhibitors. The active ouabain inhibitable transport of Na ion and K ion will be defined in lymphocytes as an example of an energy utilizing process. Cation content will be measured by flame photometry and transport through the use of radioactive isotopes - Na24 and K42. The effect of inhibition of energy producing steps on cation transport will be measured, and conversely the effect of transport inhibition on energy production will be determined. Inhibitors such as ouabain and oligomycin will be employed to block cation transport, and the effect on blastic transformation with its concomitant increase in RNA, DNA, and protein synthesis assessed. Since leukemic cells have a slower response to mitogenic agents, this area of investigation will clarify potential differences in energy production, energy specificity, and metabolic control mechanisms in normal and leukemic lymphocytes. Basic cellular information of this type hopefully will suggest methods for metabolic alteration of malignant cells to either correct critical defects or accelerate their demise.